AXAFA – AFNET 5: AF ablation with Apixaban or VKA is safe and may have a positive effect on cognitive function

20.03.2018

Atrial fibrillation ablation with continuous Apixaban does not increase the risk of stroke or bleeding compared to vitamin K antagonists and may have a positive effect on cognitive function. These are the key findings from the investigator-initiated clinical trial AXAFA – AFNET 5. The results are presented at the EHRA congress in Barcelona, Spain, today [1, 2].

The international chief investigator of the AXAFA – AFNET 5 trial, Prof. Paulus Kirchhof of the University of Birmingham, UK, describes the medical need behind the trial: “Catheter ablation is being used increasingly to treat patients with symptomatic atrial fibrillation, but the procedure leaves patients at a certain risk of stroke, bleeding, and clinically silent acute brain lesions. We also know that thrombotic events can impair cognitive function.” The president of the European Heart Rhythm Association (EHRA), Prof. John Camm, St. George’s University, London, UK, adds: “In the last five years, research has shown that continuous anticoagulation treatment reduces the peri-procedural stroke risk in AF ablation patients. The NOACs Rivaroxaban and Dabigatran have been shown to be at least as effective as warfarin in this setting [4, 5], but we didn’t have data on the use of Apixaban.”

In the 1:1 randomised AXAFA – AFNET 5 trial, 633 patients in Europe and the USA received either continuous Apixaban or a VKA. “In contrast to the prior studies,” explains Prof. Kirchhof, “all the patients in AXAFA – AFNET 5 had risk factors for stroke, resulting in a mean age of 64 years which is four years older than in other AF ablation trials.”

Prof. Kirchhof notes: “The bleeding rate was half of what we have expected, with 22 patients experiencing events on Apixaban, and 23 on VKAs, and there was a remarkably low rate of stroke, with only two events being observed in the trial (0.3%). In addition, seven episodes of cardiac tamponade – two with Apixaban and five with a VKA – were managed with drainage, without the need for antidotes.”

Using the Montreal Cognitive Assessment test the investigators found a small but statistically significant improvement in cognitive function in both study groups at the end of the study.

Another unique feature of the AXAFA-AFNET 5 trial is the use of brain magnetic resonance imaging (MRI) in more than half of the study patients within 48 hours after ablation to quantify procedure-related acute ischaemic brain lesions. The results of the brain MRI substudy demonstrated no significant difference in clinically silent acute brain lesions between the treatment arms.

"This trial is very important since it demonstrated as we did with warfarin that uninterrupted anticoagulation strategy with Apixaban in patients with AF and high stroke risk undergoing ablation is feasible" says Luigi Di Biase from Montefiore-Einstein Center, New York, USA, co-principal investigator.

“AXAFA – AFNET 5 confirms that continuous NOAC therapy is safe during atrial fibrillation ablation, supporting the findings from the prior studies and demonstrating that the safety of this approach extends to elderly patients at a risk of stroke,” says Prof. Stephan Willems, University Heart Center, Hamburg, Germany, one of the investigators of the RE-CIRCUIT trial [5]. “More than that,” he continues, “because the type of VKA and catheter ablation technique selected was the choice of the local investigators, a variety of agents and techniques were used. This highlights the applicability of the results to continuous anticoagulation across different clinical practices.”

Prof. Kirchhof feels sure that the results will have a big impact on treatment: “The results of AXAFA – AFNET 5 will go a long way towards reassuring clinicians that continuous Apixaban is a safe and effective alternative to VKA for patients undergoing atrial fibrillation ablation, even those at risk of stroke.”

AFNET board member Prof. Ulrich Schotten, Maastricht University, Maastricht, NL, concludes: “AXAFA – AFNET 5 is one of the clinical trials initiated and conducted by the AFNET and supported by the DZHK in a unique cooperation. We are proud of this ongoing partnership, and remain confident that the other ongoing AFNET trials will also provide valuable results to answer important questions in the field of atrial fibrillation.”

The German Atrial Fibrillation NETwork (AFNET) initiated and conducted the AXAFA – AFNET 5 trial. The study was partially funded by the German Centre for Cardiovascular Research (DZHK). Financial support was provided by Bristol-Myers Squibb and Pfizer.

The Atrial Fibrillation NETwork (AFNET) is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and the USA. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK).